21-42409539-C-T

Variant names:

• chr21-42409539-C-T
• rs139067853
• NM_018961.4:c.285C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_018961.4(UBASH3A):​c.285C>T​(p.Ser95Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: UBASH3A NM_018961.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

Genes affected

UBASH3A (HGNC:12462): (ubiquitin associated and SH3 domain containing A) This gene encodes one of two family members belonging to the T-cell ubiquitin ligand (TULA) family. Both family members can negatively regulate T-cell signaling. This family member can facilitate growth factor withdrawal-induced apoptosis in T cells, which may occur via its interaction with AIF, an apoptosis-inducing factor. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-42409539-C-T is Benign according to our data. Variant chr21-42409539-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3030883.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	NM_018961.4	MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 15	NP_061834.1	P57075-1
	UBASH3A	NM_001001895.3		c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 14	NP_001001895.1	P57075-2
	UBASH3A	NM_001243467.2		c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 12	NP_001230396.1	P57075-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3A	ENST00000319294.11	TSL:1 MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 15	ENSP00000317327.6	P57075-1
	UBASH3A	ENST00000291535.11	TSL:1	c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 14	ENSP00000291535.6	P57075-2
	UBASH3A	ENST00000398367.1	TSL:1	c.285C>T	p.Ser95Ser	synonymous	Exon 3 of 12	ENSP00000381408.1	P57075-3

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251464 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74320

African (AFR) AF: 0.000290 AC: 12 AN: 41424

American (AMR) AF: 0.000327 AC: 5 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UBASH3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.51
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139067853; hg19: chr21-43829648;